Pituitary tumor-transforming gene expression is a prognostic marker for tumor recurrence in squamous cell carcinoma of the head and neck

Abstract

Background: The proto-oncogene pituitary tumor-transforming gene (PTTG) has been shown to be abundantly overexpressed in a large variety of neoplasms likely promoting neo-vascularization and tumor invasiveness. In this study, we investigated a potential role for PTTG mRNA expression as a marker to evaluate the future clinical outcome of patients diagnosed with primary cancer of the head and neck.

Methods: Tumor samples derived from primary tumors of 89 patients suffering from a squamous cell carcinoma were analyzed for PTTG mRNA-expression and compared to corresponding unaffected tissue. Expression levels were correlated to standard clinico-pathological parameters based on a five year observation period.

Results: In almost all 89 tumor samples PTTG was found to be overexpressed (median fold increase: 2.1) when compared to the unaffected tissue specimens derived from the same patient. The nodal stage correlated with PTTG transcript levels with significant differences between pN0 (median expression: 1.32) and pN+ (median expression: 2.12; P = 0.016). In patients who developed a tumor recurrence we detected a significantly higher PTTG expression in primary tumors (median expression: 2.63) when compared to patients who did not develop a tumor recurrence (median expression: 1.29; P = 0.009). Since the median expression of PTTG in patients with tumor stage T1/2N0M0 that received surgery alone without tumor recurrence was 0.94 versus 3.82 in patients suffering from a tumor recurrence (P = 0.006), PTTG expression might provide a feasible mean of predicting tumor recurrence.

Conclusion: Elevated PTTG transcript levels might be used as a prognostic biomarker for future clinical outcome (i.e. recurrence) in primary squamous cell carcinomas of the head and neck, especially in early stages of tumor development.

Figure 1

Expression of PTTG mRNA in HNSCC tumor samples. Total RNA (2 μg) underwent electrophoresis, transferred to positively charged nylon membranes and probed with PTTG specific probe (TA = T2N0M0/no recurrence, TB = T4N1M0/recurrence, TC = T3N2M0/no recurrence, TD = T2N0M0/recurrence, N indicates the corresponding normal tissue). Bottom of panel (a) shows the corresponding β-Actin signal after stripping and re-hybridization procedure. (b) Distribution of normalized PTTG expression levels in all (n = 89) analyzed tumor samples.

Figure 2

Distribution of PTTG expression in primary tumors with different pN stages. Boxplot shows PTTG expression of all analyzed primary tumors (n = 89) grouped to their corresponding pN-stages (a). The pN-stage correlated to PTTG expression level with a significance of P = 0.021. Thereby significant (P = 0.016) differences between the pN0 (n = 25, negative) and pN+ (n = 64, positive) staged patients could be detected (b).

Figure 3

PTTG mRNA expression in primary tumors of patients with tumor recurrences. (a) Boxplot shows the PTTG expression in primary tumors of all patients (n = 89) who suffered from a recurrence (positive, n = 49) versus the patients who did not develop a recurrence (negative, n = 40) within the 5-years observation period (P = 0.009). Boxplot (b) shows the distribution of PTTG mRNA levels in primary tumors in comparison to those levels in tumors of pN0 (n = 25) staged patients with (positive) and without (negative) a tumor recurrence (P = 0.006).

Figure 4

Immunhistochemical analysis of PTTG. Exemplary PTTG staining of a primary tumor of a patient (pT1N0M0), who did not develop a tumor recurrence within the observation period (a). Staining of a primary tumor of a patient (pT1N0M0) who developed a tumor recurrence 24 months after primary tumor resection (c). (e) PTTG staining in the tumor recurrence of the same patient. (b, d and f) corresponding control sections after IgG staining.